Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans

Feb 27, 2021Journal of pineal research

Night shift work disrupts daily DNA repair rhythms and increases DNA damage in people

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Abstract

Simulated night shift work significantly altered the circadian rhythm of cancer-related genes.

Circadian disruption is linked to an increased risk of various health disorders, including cancer.
The study examined how night shift work affects cancer hallmark pathway genes in healthy young adults.
Genes involved in DNA repair showed rhythmic changes after a simulated day shift but not after a simulated night shift.
Increased sensitivity to DNA damage was observed following exposure to simulated night shifts.
Circadian dysregulation of DNA repair processes may contribute to the elevated cancer risk in night shift workers.

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Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24-hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.

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Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans

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